Target for breaking defenses of ‘superbugs’ discovered

LONDON – Scientists in Britain have found how drug-resistant bacteria build and maintain a defensive wall — a discovery that paves the way for the development of drugs to break through the barrier and kill the often-deadly “superbugs.”

In recent decades, bacteria resistant to multiple drugs, such as methicillin-resistant Staphylococcus aureus (MRSA) or Clostridium difficile, have grown into a global health threat, while superbug strains of infections like tuberculosis and gonorrhea have become untreatable.

The World Health Organization has warned that many antibiotics could become useless this century, leaving patients vulnerable to deadly infections and threatening the future of medicine.

Researchers publishing a study in the journal Nature on Monday said knowing the mechanism bacteria use to keep up their defenses brings scientists closer to solving the problem of antibiotic resistance, since new treatments can be designed to weaken those defenses rather than attack the bacteria directly.

This means that in the future, bacteria may not develop drug resistance at all, they said.

The team, led by Changjiang Dong, a professor at Britain’s University of East Anglia, used a machine called Diamond Light Source — which produces light 10 billion times brighter than the sun — to investigate in tiny detail a class of bugs known as Gram-negative bacteria.

Gram-negative bacteria are particularly resistant to antibiotics because their cells have an impermeable lipid-based outer membrane that acts as a defensive barrier against attacks from the body’s immune system and from antibiotic drugs.

Dong’s team zeroed in on the defensive wall and found that it is built and maintained by what they described as a beta-barrel assembly machinery (BAM) containing five sub-units called BamA, BamB, BamC, BamD and BamE.

They then figured out how these subunits work together to form and maintain the cell membrane, and how to disrupt that mechanism.

“The beta-barrel assembly machinery is responsible for building the ‘gates’ in the cell wall,” Dong explained. “Stopping the beta-barrel assembly machine from building the gates in the cell wall causes the bacteria to die.”

The study found that the subunit BamA, which is found in the outer membrane and exposed to the outer side of the bacteria, is a key component of the mechanism — making it “a great target” for new drugs, Dong’s team said.